Adrenergic innervation of cerebral microvessels has been implicated in the regulation of cerebral blood flow (CBF) and permeability of blood-brain barrier (BBB). In support of this contention was the demonstration of catecholaminergic receptors linked to adenylate cyclase (AC) in themicrovessels and in the cultured cerebrovascular endothelium. Since the control of CBF most likely is not only confined to the endothelium, we investigated the responsiveness of cerebrovascular smooth muscle cell AC to catecholamines. These studies have shown that the catecholamine analogues, zinterol and isoproterenol, were more effective in the stimulation of AC activity than epinephrine and norepinephrine. When the selective antagonists for Beta1 and Beta2 receptors (Beta1-type practolol and isoproterenol, epinephrine and norepinephrine stimulation of AC activity, the Beta1 in contrast to Beta2 antogonists were found ineffective. The Alpha-blockers (phentolamine Alpha1/Alpha2-type antagonists) and yohimbine (Alpha2-type antagonist) alone or in the presence of propranolol had not significantly inhibited the catecholamine-induced enhancement of cAMP formation. On the other hand, prazosine (Alpha1-type antagonist) blocked the stimulatory effect of epinephrine and norepinephrine on AC system. Similarly, the Alpha2-agonist, clonidine, did not affect the catecholamines' stimulated AC activity while Alpha1 agonist, phenylephrine, induced a synergistic enhancement of norepinephrine production of cAMP. The findings of Beta2- and Alpha1-type adrenergic receptors in the cultured cerebrovascular smooth muscle provide additional support for the implicated involvement of adrenergic innervation in the regulation of CBF and BBB permeability.